Devices and methods for biochip multiplexing

• US 20110180425A1
• Filed: 10/31/2007
• Published: 07/28/2011
• Est. Priority Date: 04/21/1999
• Status: Abandoned Application

• Current Assignee: Roche Molecular Systems Inc (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Kayyem, Jon Faiz
• Application Number:
  US11/982,368
• Publication Number:
  US 20110180425A1
• Time in Patent Office: Days
• US Class Current: 205/780.5
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0611 duck bill valves
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 35/00 : Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: B82Y 40/00 : Manufacture or treatment of nanostructures
• CPC Class Codes: C12Q 1/6813 : Hybridisation assays
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2563/113 : the label being electroactive, e.g. redox labels
• CPC Class Codes: C12Q 2565/629 : being a microfluidic device
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2610/00 : Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 27/3275 : Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: G01N 27/3276 : being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 27/4473 : by electric means
• CPC Class Codes: G01N 27/44752 : Controlling the zeta potential, e.g. by wall coatings
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: G01N 33/54386 : Analytical elements

Abstract

The invention is directed to devices that allow for simultaneous multiple biochip analysis. In particular, the devices are configured to hold multiple cartridges comprising biochips comprising arrays such as nucleic acid arrays, and allow for high throughput analysis of samples.

Claims

1-14. -14. (canceled)

15. A method of analyzing a biochip comprising:

a) providing a biochip comprising;

i) an array of detection electrodes, and

ii) a plurality of different hybridization complexes each comprising a ligand, a ligand-specific analyte and an electrochemical detection label at least one of which is different as between said different hybridization complexes; and

b) detecting said labels as a measure of the presence or identity of said different hybridization complexes.

16. The method of claim 15 comprising using a plurality of different electrochemical detection labels of different electrochemical potential to measure the presence or identity of different ligand-specific analytes.

17. The method of claim 15 wherein one or more of said labels comprises a multimer of the same label covalently bound to the same member of a hybridization complex.

18. The method of claim 16 or 17 wherein said different labels comprises a member selected from the group consisting of ferrocene and ferrocene derivatives.

19. The method of claim 15 wherein at least one of said ligands comprises a member selected from the group consisting of nucleic acids and nucleic acid analogs.

20. The method of claim 15 wherein at least one of said ligands comprises a member selected from the group consisting of peptides and proteins.

21. The method of claim 20 wherein at least one of said ligands comprises an antibody or portion thereof.

22. The method of claim 15 wherein said detecting step comprises detecting a plurality of different target analytes simultaneously using a plurality of different binding ligands.

23. The method of claim 22 wherein said plurality of different ligands comprises different nucleic acid sequences.

24. The method of claim 23 wherein said different nucleic acid sequences are each associated with different electrodes.

25. The method of claim 22 wherein said plurality of target analytes comprises both nucleic acids and non nucleic acids.

26. The method of claim 19 wherein said analytes comprise amplified nucleic acids.

27. The method of claim 26 wherein said analytes are amplified on-chip.

28. The method of claim 26 wherein said amplified nucleic acids are amplified using PCR.

29. The method of claim 15 wherein at least one of said analytes or ligands is associated with a genetic disease.

30. The method of claim 15 wherein at least one of said analytes or ligands is associated with an infectious disease.

31. The method of claim 19 wherein at least one of said ligands is a nucleic acid analog selected from the group consisting of peptide nucleic acids and analogs having positively charged backbones.

33. The method of claim 15 wherein a plurality of detection electrodes in said array are independently addressable.

34. The method of claim 15 wherein said biochip further comprises a memory chip or barcode and wherein said method further comprises reading said memory chip or barcode.

35. The method of claim 15 wherein said detecting comprises transmission of a signal to a processor and filtering or amplifying said signal.

36. The method of claim 15 further comprising adding said analytes to said biochip in the form of blood, tissue, sputum or saliva sample, and then processing said sample on-chip.

32. A method of analyzing a biochip comprising:

a) providing a biochip comprising;

i) an array of detection electrodes, and

ii) a plurality of different hybridization complexes each comprising a ligand, a ligand-specific analyte and an electrochemical detection label, said label comprised of a transition metal or metal, and at least one of which said ligand, said ligand-specific analyte, and said electrochemical detection label is different as between said different hybridization complexes; and

b) detecting said labels as a measure of the presence or identity of said different hybridization complexes.

37. A method of analyzing a biochip comprising:

a) providing a biochip comprising;

i) an array of detection electrodes, and

ii) a plurality of different hybridization complexes each comprising a ligand, a ligand-specific analyte and an electrochemical detection label at least one of which said is different as between said different hybridization complexes;

b) circulating and recirculating an aqueous sample comprising one or more of said ligand, said ligand-specific analyte, and said electrochemical detection label across said array in said biochip; and

c) detecting said labels as a measure of the presence or identity of said different hybridization complexes.

38. A method of analyzing a biochip comprising:

a) providing a biochip comprising;

i) an array of detection electrodes, and

ii) a plurality of different hybridization complexes each comprising a ligand, a ligand-specific analyte and an electrochemical detection label at least one of which said is different as between said different hybridization complexes; and

b) detecting said labels as a measure of the presence or identity of said different hybridization complexes using one or more of AC voltametry, DC voltametry, digital lock-in, Fourier transform and joint time-frequency transformation.

39. A method of analyzing a biochip comprising:

a) providing a biochip comprising;

i) an array of detection electrodes;

ii) a reference electrode;

iii) one or more auxiliary electrodes; and

iv) a plurality of different hybridization complexes each comprising a ligand, a ligand-specific analyte and an electrochemical detection label at least one of which said is different as between said different hybridization complexes; and

b) detecting said labels as a measure of the presence or identity of said different hybridization complexes.